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Open Access 01-07-2017 | Original

Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net

Authors: Jean-François Timsit, Marlieke E. A. de Kraker, Harriet Sommer, Emmanuel Weiss, Esther Bettiol, Martin Wolkewitz, Stavros Nikolakopoulos, David Wilson, Stephan Harbarth, on behalf of the COMBACTE-NET consortium

Published in: Intensive Care Medicine | Issue 7/2017

Abstract

Purpose

In this era of rising antimicrobial resistance, slowly refilling antibiotic development pipelines, and an aging population, we need to ensure that randomized clinical trials (RCTs) determine the added benefit of new antibiotic agents effectively and in a valid way, especially for severely ill patients. Unfortunately, universally accepted endpoints for the evaluation of new drugs in severe infections are lacking.

Methods

We review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches.

Results

Usual endpoints actually recommended for drug development suffer from important flaws. Mortality requires large sample size and only partly related to the infectious process. Clinical cure rate is highly subjective in critically ill patients where symptoms may be related to other intercurrent events. Currently, composite endpoints, hierarchical nested designs, and competing risks analysis seem to be the most promising new tools for designing and analyzing clinical trials in this area, although they require further validation.

Conclusion

Regulatory authorities, pharmaceutical companies, and clinicians need to agree on the most appropriate clinical endpoints for severe infections to ensure efficient approval of new, effective antibiotic agents.

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Title: Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net
Authors: Jean-François Timsit
Marlieke E. A. de Kraker
Harriet Sommer
Emmanuel Weiss
Esther Bettiol
Martin Wolkewitz
Stavros Nikolakopoulos
David Wilson
Stephan Harbarth
on behalf of the COMBACTE-NET consortium
Publication date: 01-07-2017
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 7/2017
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-017-4802-4

At a glance: The STEP trials

Springer Medicine

Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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